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Sökning: id:"swepub:oai:DiVA.org:oru-27894" > Adaptive immune res...

Adaptive immune response in the intestinal mucosa of microscopic colitis patients

Kumawat, Ashok Kumar, 1982- (författare)
Örebro universitet,Institutionen för hälsovetenskap och medicin
Hultgren-Hörnquist, Elisabeth, Professor (preses)
Örebro universitet,Institutionen för läkarutbildning
Bohr, Johan (preses)
Örebro universitet,Institutionen för hälsovetenskap och medicin
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Tysk, Curt, Professor (preses)
Universitetssjukhuset Örebro
Sirsjö, Allan, Professor (preses)
Örebro universitet,Institutionen för hälsovetenskap och medicin
Lundin, Samuel, Professor (opponent)
Inst för biomedicin, Sahlgrenska akademin, Göteborgs universitet
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 (creator_code:org_t)
ISBN 9789176689295
Örebro : Örebro universitet, 2013
Engelska 83 s.
Serie: Örebro Studies in Medicine, 1652-4063 ; 84
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
Abstract Ämnesord
Stäng  
  • Microscopic colitis (MC) is a chronic diarrhoeal disease of unknown aetiology, comprising collagenous colitis (CC) and lymphocytic colitis (LC). The nature of the adaptive local immune responses in the mucosa of MC patients is however far from elucidated. The present study investigates phenotypic and functional characteristics of the adaptive local immune responses in the colonic mucosa of these patients.Our immunohistochemistry and flow cytometry studies (Paper I & II) demonstrated increased frequencies of CD8+ T cells in the colonic epithelium and lamina propria of both LC and CC patients compared to controls, whereas the frequencies of CD4+ T cells were unaltered or reduced. Our flow cytometry data revealed increased local activation of both CD4+ and CD8+ T cells in the lamina propria as well as the intraepithelial compartment of CC and LC patients compared to controls, demonstrated as increased proportions of these cells expressing the active/memory marker CD45RO and the proliferation marker Ki67.Analysis of recent thymic emigrants by measuring T cell receptor excision circle (TREC) levels in the colonic mucosa of CC and LC patients revealed reduced TRECs levels in these patients compared to controls (Paper III). These results suggests that the observed increased numbers of T cells in the mucosa of CC and LC patients is due to the expansion of local resident T cells rather than direct recruitment of recent thymic emigrants to the mucosa.Molecular analysis of T helper (Th) cell and cytotoxic T lymphocyte (Tc) mucosal cytokines at messenger and protein levels in the colonic biopsies from CC and LC patients demonstrated a mixed Th17/Tc17 and Th1/Tc1 mucosal cytokine profile and revealed significant differences in the mucosal cytokine levels in CC and LC patients compared to controls (Paper IV).Finally, we have set up an in vitro model to investigate how the colonic milieu affects the activation and differentiation of T lymphocytes (Paper V). Our preliminary data indicate increased production of both pro inflammatory and antiinflammatory cytokines by peripheral blood T cells in the presence of soluble factors from the inflamed colonic mucosa of CC patients compared to controls.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Gastroenterologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Biomedicinsk laboratorievetenskap/teknologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Biomedical Laboratory Science/Technology (hsv//eng)

Nyckelord

Microscopic colitis
collagenous colitis
lymphocytic colitis
intraepithelial lymphocytes
lamina propria lymphocytes
T cell receptor excision circle
T helper cells
cytotoxic T lymphocyte and mucosal cytokines
Biomedicin
Biomedicine

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